Clinical signiﬁcance of altering epithelial–mesenchymal transition
in metastatic lymph nodes of gastric cancer
Received: 29 December 2016 / Accepted: 18 February 2017 / Published online: 28 February 2017
Ó The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2017
Background The E-cadherin, N-cadherin, and Snail genes are
epithelial–mesenchymal transition (EMT)-inducible genes.
Previous studies demonstrated that the expression of EMT
markers in the primary tumor sites of gastric cancer correlates
with tumor progression and prognosis. However, the clinical
signiﬁcance of the expression of these EMT markers in meta-
static lymph nodes remains unclear. In the present study, we
investigated the expression of these EMT markers in the pri-
mary tumor sites and metastatic lymph nodes.
Methods Immunohistochemistry was used to investigate
the expression of E-cadherin, N-cadherin, and Snail in 89
primary tumors and 511 metastatic lymph nodes obtained
from patients with gastric cancer.
Results The weak expression of E-cadherin in tumors and
lymph nodes increased with more lymph node metastasis and
in more undifferentiated tumors. The strong expression of
N-cadherin in lymph nodes correlated with more lymph nodes
metastasis, an advanced stage, and poor prognosis. The weak
expression of Snail in tumors correlated with lymphatic
invasion. The strong expression of Snail in lymph nodes
correlated with more lymph node metastasis and an advanced
stage. The strong expression of Snail in tumors and its weak
expression in lymph nodes correlated with more lymph node
metastasis, an advanced stage, and poor prognosis.
Conclusions The expression of N-cadherin in metastatic
lymph nodes is useful for predicting the prognosis of patients
with gastric cancer. The Snail switch—namely, the positive-
to-negative conversion of the Snail status—between primary
tumors and lymph node metastasis may be important for
conﬁrming EMT and mesenchymal–epithelial transition.
Keywords Epithelial–mesenchymal transition Á
Gastric cancer Á Metastatic lymph nodes Á Snail switch
Gastric cancer is one of the commonest malignancies, and
patients with advanced gastric cancer have a poor prognosis .
Recent studies clearly demonstrate that epithelial–mesenchy-
mal transition (EMT), a developmental process in which
epithelial cells lose intercellular adhesion and myoﬁbroblastic
features, plays an important role in tumor progression and
metastasis [2–5]. Signiﬁcant changes occur during EMT,
including the downregulation of epithelial markers such as
E-cadherin and upregulation of mesenchymal markers such as
N-cadherin [6–9]. A switch in cadherin from the loss of
E-cadherin to gain of N-cadherin is part of the EMT process.
Snail, Slug, and Twist are some of the transcription
factors that govern EMT . Snail was previously reported
to be important during EMT in several carcinomas,
including non-small-cell lung carcinomas, ovarian carci-
nomas, urothelial carcinomas, esophageal squamous cell
carcinomas, and gastric adenocarcinomas [10–14]. Natsu-
goe et al.  and Shin et al.  reported that overex-
pression of Snail in the main tumors of esophageal
Electronic supplementary material The online version of this
article (doi:10.1007/s10120-017-0705-x) contains supplementary
material, which is available to authorized users.
& Keishi Okubo
Department of Digestive Surgery, Breast and Thyroid
Surgery, Field of Oncology, Kagoshima University Graduate
School of Medical and Dental Sciences, 8-35-1 Sakuragaoka,
Kagoshima 890-8520, Japan
Molecular Frontier Surgery, Kagoshima University Graduate
School of Medical and Dental Sciences, Kagoshima, Japan
Gastric Cancer (2017) 20:802–810